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PNAS 97 (14): 7835-7840

Copyright © 2000 by the National Academy of Sciences.

Cell Biology
 Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3- 3-dependent cellular localization

Christina M. Grozinger and Stuart L. Schreiber*

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138

Contributed by Stuart L. Schreiber, May 3, 2000

Transcription is controlled in part by the dynamic acetylation and deacetylation of histone proteins. The latter process is mediated by histone deacetylases (HDACs). Previous analysis of the regulation of HDAC activity in transcription has focused primarily on the recruitment of HDAC proteins to specific promoters or chromosomal domains by association with DNA-binding proteins. To characterize the cellular function of the recently identified HDAC4 and HDAC5 proteins, complexes were isolated by immunoprecipitation. Both HDACs were found to interact with14-3-3 proteins at three phosphorylation sites. The association of 14-3-3 with HDAC4 and HDAC5 results in the sequestration of these proteins in the cytoplasm. Loss of this interaction allows HDAC4 and HDAC5 to translocate to the nucleus, interact with HDAC3, and repress gene expression. Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins.

* To whom reprint requests should be addressed. E-mail: sls{at}slsiris.harvard.edu.

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S. C. Galasinski, K. A. Resing, J. A. Goodrich, and N. G. Ahn (2002)
J. Biol. Chem. 277, 19618-19626
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Histone Deacetylase 5 Is Not a p53 Target Gene, But Its Overexpression Inhibits Tumor Cell Growth and Induces Apoptosis.
Y. Huang, M. Tan, M. Gosink, K. K. W. Wang, and Y. Sun (2002)
Cancer Res. 62, 2913-2922
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Modulation of p53, ErbB1, ErbB2, and Raf-1 Expression in Lung Cancer Cells by Depsipeptide FR901228.
X. Yu, Z. S. Guo, M. G. Marcu, L. Neckers, D. M. Nguyen, G. A. Chen, and D. S. Schrump (2002)
J Natl Cancer Inst 94, 504-513
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Functional Divergence between Histone Deacetylases in Fission Yeast by Distinct Cellular Localization and In Vivo Specificity.
P. Bjerling, R. A. Silverstein, G. Thon, A. Caudy, S. Grewal, and K. Ekwall (2002)
Mol. Cell. Biol. 22, 2170-2181
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